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[抗癌剂敏感性试验的研究,特别参考双层集落形成试验]

[Studies on the sensitivity test of anticancer agents with special reference to double layer colony forming assay].

作者信息

Ohsaki Y, Fujikane T, Shimizu T

出版信息

Hokkaido Igaku Zasshi. 1984 Nov;59(6):762-74.

PMID:6543356
Abstract

The necessity to assess the effect of chemotherapeutic agents on the patients beforehand treatment has been stressed. In 1977, Salmon & Hamburger developed a new method to evaluate the drug sensitivity using cell suspension derived from the patients. They called the method as "human tumor stem cell assay". Since then, many reports were published about the correlation between the clinical outcomes and the results of human tumor stem cell assay, and high relationship between them was documented. The present study was undertaken to evaluate the method using the modified system; double layer colony forming assay, cell growth curve, tritiated thymidine uptake and flow cytometry. The drugs used in this study were adriamycin (ADR) and cis-platinum (C-DDP). We chose the human small cell lung cancer cell line PC-6 as a target cell. The conclusions are follows. The effects of ADR and C-DDP were concentration dependent respectively. The time dependent effect of C-DDP on PC-6 was revealed by enhancement of lethal effect, when they were exposed to the drug for 24 hours. A possibility exists that reproductive death would take place among PC-6 by ADR, along with DNA injury. It is one of the explanations for reduction of colony formation in contrast to increase in cell number. The effect of C-DDP on PC-6 was diminished with time. This phenomenon was reflected on double layer colony forming assay, and was possible explanation for reduction of colony formation which was greater than that of expected from cell growth curve.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

事先评估化疗药物对患者治疗效果的必要性已得到强调。1977年,萨蒙和汉堡开发了一种使用患者来源的细胞悬液评估药物敏感性的新方法。他们将该方法称为“人肿瘤干细胞检测”。从那时起,发表了许多关于临床结果与人肿瘤干细胞检测结果之间相关性的报告,并且记录了它们之间的高度相关性。本研究旨在使用改良系统评估该方法;双层集落形成试验、细胞生长曲线、氚标记胸腺嘧啶核苷摄取和流式细胞术。本研究中使用的药物是阿霉素(ADR)和顺铂(C-DDP)。我们选择人小细胞肺癌细胞系PC-6作为靶细胞。结论如下。阿霉素和顺铂的作用分别呈浓度依赖性。当PC-6细胞暴露于顺铂24小时时,顺铂对其的时间依赖性作用通过致死效应的增强得以体现。阿霉素可能会导致PC-6细胞发生增殖性死亡,并伴有DNA损伤。这是集落形成减少而细胞数量增加的一种解释。顺铂对PC-6细胞的作用随时间减弱。这种现象在双层集落形成试验中得到体现,并且可能是集落形成减少大于细胞生长曲线预期减少的原因。(摘要截选至250字)

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